Angiotensin II and III are potent stimuli to aldosterone release in the adrenal and to prostaglandin release in the vasculature. The prostaglandins also stimulate steroidogenesis in the adrenal. Additionally, the steroidogenic activity of the angiotensins is inhibited by drugs which block the synthesis of prostaglandins, indomethacin and meclofenamate. This proposal will examine the possibility that the angiotensins stimulate the release of adrenal prostaglandins and that these prostaglandins augment or modulate angiotensin-induced aldosterone release. These studies will be performed in vitro in rat adrenal capsular cell suspension. The adrenal production of prostaglandins will be determined with radiochemical methods using high-performance liquid chromatography and with specific radioimmunoassays. Some studies will be repeated in vivo in conscious rats. Four possibilities will be examined: 1) the possibility that PGI2 augments of the steroidogenic activity of the angiotensins. This is based on preliminary evidence that AII releases PGI2 but not PGE2 in steroidogenic doses and that PGI2 is greater than 100 times more potent than PGE2 in stimulating steroidogenesis. 2) Since the adrenal contains equal amounts of adrenic acid and arachidonic acid and since these fatty acids are converted to C-22 and C-20 prostaglandins, respectively, the possibility that adrenic acid and its C-22 prostaglandins augment angiotensin-induced steroidogenesis will be examined. Interestingly, adrenic acid is a more potent steroidogenic agent than arachidonic acid. 3) The lipoxygenase and cyclooxygenase inhibitor ETYA stimulates basal and AII-stimulated steroid-ogenesis while the cyclooxygenase inhibitor indomethacin inhibits both responses. This finding suggests the third possibility that a lipoxygenase product is formed in the adrenal that is inhibitory to aldosterone release. 4) Finally, since extracellular calcium is necessary for the steroidogenic activity of AII and since indomethacin is a calcium antagonist, the possibility that indomethacin inhibits angiotensin induced steroidogenesis through calcium antagonism will be examined. These studies will clarify the intra-adrenal mechanism involved in the control of basal and angiotensin-induced aldosterone release.